chr1-237456592-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The ENST00000366574.7(RYR2):c.1477-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,288,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
ENST00000366574.7 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.1477-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000366574.7 | NP_001026.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.1477-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001035.3 | ENSP00000355533 | P1 | |||
RYR2 | ENST00000659194.3 | c.1477-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENSP00000499653 | ||||||
RYR2 | ENST00000660292.2 | c.1477-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENSP00000499787 | ||||||
RYR2 | ENST00000609119.2 | c.1477-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 | ENSP00000499659 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 4AN: 143328Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.0000220 AC: 4AN: 181542Hom.: 0 AF XY: 0.0000200 AC XY: 2AN XY: 99966
GnomAD4 exome AF: 0.0000124 AC: 16AN: 1288454Hom.: 0 Cov.: 39 AF XY: 0.0000143 AC XY: 9AN XY: 630522
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000279 AC: 4AN: 143328Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 2AN XY: 69284
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 21, 2015 | c.1477-8C>T in intron 15 of RYR2: This variant is not expected to have clinical significance because a C>T change at this position does not diverge from the sp lice consensus and is therefore unlikely to impact splicing. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 16, 2018 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at